title: Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss.
abstract: We used an exome-sequencing strategy and identified an allelic series of NOTCH2 mutations in Hajdu-Cheney syndrome, an autosomal dominant multisystem disorder characterized by severe and progressive bone loss. The Hajdu-Cheney syndrome mutations are predicted to lead to the premature truncation of NOTCH2 with either disruption or loss of the C-terminal proline-glutamate-serine-threonine-rich proteolytic recognition sequence, the absence of which has previously been shown to increase Notch signaling.
authors.affiliation: Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Simpson
authors.forename: Melita D
authors.initials: MD
authors.lastname: Irving
authors.forename: Esra
authors.initials: E
authors.lastname: Asilmaz
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Gray
authors.forename: Dimitra
authors.initials: D
authors.lastname: Dafou
authors.forename: Frances V
authors.initials: FV
authors.lastname: Elmslie
authors.forename: Sahar
authors.initials: S
authors.lastname: Mansour
authors.forename: Sue E
authors.initials: SE
authors.lastname: Holder
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Brain
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Burton
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Kim
authors.forename: Richard M
authors.initials: RM
authors.lastname: Pauli
authors.forename: Salim
authors.initials: S
authors.lastname: Aftimos
authors.forename: Helen
authors.initials: H
authors.lastname: Stewart
authors.forename: Chong Ae
authors.initials: CA
authors.lastname: Kim
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder-Espinasse
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Robertson
authors.forename: William M
authors.initials: WM
authors.lastname: Drake
authors.forename: Richard C
authors.initials: RC
authors.lastname: Trembath
mesh_terms: D000483:Alleles; D001483:Base Sequence; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005260:Female; D031845:Hajdu-Cheney Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010375:Pedigree; D021382:Protein Sorting Signals / Q000235:genetics; D051883:Receptor, Notch2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D050505:Mutant Proteins; C497764:NOTCH2 protein, human; D021382:Protein Sorting Signals; D051883:Receptor, Notch2